Ligand binding in the catalytic antibody 17E8. A free energy perturbation calculation study

Thomas Fox; Thomas S. Scanlan; Peter A. Kollman

doi:10.1021/ja964315j

Ligand binding in the catalytic antibody 17E8. A free energy perturbation calculation study

Thomas Fox, Thomas S. Scanlan, Peter A. Kollman

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38 Scopus citations

Abstract

We present free energy calculations on the Michaelis complexes of the catalytic antibody 17E8 with two substrates, which differ only in their side chains. Replacing a -CH₂- group with a -S- increases K(M) by a factor of about 5-8. This corresponds to a free energy 'preference' for the -CH₂- ligand of about 0.9-1.3 kcal/mol. The calculations semiquantitatively reproduce the experimental free energies and show that the preference for a -CH₂- over a -S- is mainly due to the more favorable solvation free energy in the unbound form of the molecule.

Original language	English (US)
Pages (from-to)	11571-11577
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	119
Issue number	48
DOIs	https://doi.org/10.1021/ja964315j
State	Published - Dec 1 1997
Externally published	Yes

ASJC Scopus subject areas

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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title = "Ligand binding in the catalytic antibody 17E8. A free energy perturbation calculation study",

abstract = "We present free energy calculations on the Michaelis complexes of the catalytic antibody 17E8 with two substrates, which differ only in their side chains. Replacing a -CH2- group with a -S- increases K(M) by a factor of about 5-8. This corresponds to a free energy 'preference' for the -CH2- ligand of about 0.9-1.3 kcal/mol. The calculations semiquantitatively reproduce the experimental free energies and show that the preference for a -CH2- over a -S- is mainly due to the more favorable solvation free energy in the unbound form of the molecule.",

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T1 - Ligand binding in the catalytic antibody 17E8. A free energy perturbation calculation study

AU - Fox, Thomas

AU - Scanlan, Thomas S.

AU - Kollman, Peter A.

PY - 1997/12/1

Y1 - 1997/12/1

N2 - We present free energy calculations on the Michaelis complexes of the catalytic antibody 17E8 with two substrates, which differ only in their side chains. Replacing a -CH2- group with a -S- increases K(M) by a factor of about 5-8. This corresponds to a free energy 'preference' for the -CH2- ligand of about 0.9-1.3 kcal/mol. The calculations semiquantitatively reproduce the experimental free energies and show that the preference for a -CH2- over a -S- is mainly due to the more favorable solvation free energy in the unbound form of the molecule.

AB - We present free energy calculations on the Michaelis complexes of the catalytic antibody 17E8 with two substrates, which differ only in their side chains. Replacing a -CH2- group with a -S- increases K(M) by a factor of about 5-8. This corresponds to a free energy 'preference' for the -CH2- ligand of about 0.9-1.3 kcal/mol. The calculations semiquantitatively reproduce the experimental free energies and show that the preference for a -CH2- over a -S- is mainly due to the more favorable solvation free energy in the unbound form of the molecule.

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Ligand binding in the catalytic antibody 17E8. A free energy perturbation calculation study

Abstract

ASJC Scopus subject areas

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